1887

Abstract

Resistance of mice to infection with herpes simplex virus type 2 (HSV-2) is strongly dependent on the function of macrophages (Mφ). Infection of mouse Mφ with HSV-2 results in an early (4 to 10 h) activation of the cells with an enhanced respiratory burst generated after membrane triggering with a phorbol ester. The role of monokines produced during this infection was analysed. Both interferon-α/β (IFN-α/β) and tumour necrosis factor-α (TNF-α) were produced within the very first hours after infection of Mφ with HSV-2. Exogenously added IFN-α/β conferred to Mφ a respiratory burst capacity comparable to that seen after virus infection, whereas TNF-α by itself was unable to prime Mφ for a respiratory burst. In fact concentrations of TNF-α comparable to those found in HSV-2-infected Mφ cultures generally suppressed the response. However, when TNF-α was added together with IFN-α/β a dose-dependent synergistic enhancement of the IFN-induced Mφ activation was seen. The kinetics of the synergistic activation by the two monokines was similar to that seen with IFN-α/β alone. Neutralizing antibodies to IFN-α/β and TNF-α were able to diminish the HSV-induced priming of Mφ for a respiratory burst. When the two antibodies were used together in subneutralizing concentrations an additional diminution of the responsiveness was seen, indicating that both monokines are involved in the virus-induced priming of Mφ. However, high concentrations of antibodies to IFN-α/β alone were able to abolish the activation completely, whereas this was not the case with anti-TNF-α. Collectively these data demonstrate that autocrine secretion of IFN-α/β by Mφ infected with HSV-2 is a for the activation of Mφ during the infection, and that this effect of IFN is synergistically enhanced, also in an autocrine manner, by TNF-α. It is suggested that this reciprocal Mφ-monokine interaction may be of importance in resistance to virus infections.

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/content/journal/jgv/10.1099/0022-1317-74-10-2191
1993-10-01
2019-11-13
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http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-74-10-2191
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